Evidence map›Paper›PMID 25689173›Full record

ArticleToxicology and applied pharmacology2015

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.

Steven L Miller, Vassiliki Aroniadou-Anderjaska, Taiza H Figueiredo, Eric M Prager, Camila P Almeida-Suhett, James P Apland, Maria F M Braga

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicology and applied pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 24 citations in OpenAlex.

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  7. A rapidFrontiers in cellular neuroscience · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Steven L MillerDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: stevenmiller17@gmail.com.
Vassiliki Aroniadou-AnderjaskaDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: vanderjaska@usuhs.edu.
Taiza H FigueiredoDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: taiza.figueiredo.ctr@usuhs.edu.
Eric M PragerDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: eric.prager683@gmail.com.
Camila P Almeida-SuhettDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: camilapalmeida@gmail.com.
James P AplandNeurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA. Electronic address: james.p.apland.civ@mail.mil.
Maria F M BragaDepartment of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address: maria.braga@usuhs.edu.
Uniformed Services University of the Health Sciences · USDEVCOM Army Research Laboratory · US

Funding

Efficacy of GluR5 Antogonists Against Soman-Induced Seizures and NeuropathologyU01NS058162 · NINDS · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI BRAGA, MARIA F. · 2006 to 2016
$4.5M
Antiglutamatergic Therapy to Protect the Immature Brain Against Nerve AgentsU01NS102135 · NINDS · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI BRAGA, MARIA F. · 2018 to 2020
$1.3M
Targeting the Glutamatergic System to Counteract Soman Toxicity in Immature RatsR21NS094131 · NINDS · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI BRAGA, MARIA F. · 2015 to 2016
$744k
NINDS NIH HHS 5U01NS058162-07NINDS NIH HHS R21 NS094131NINDS NIH HHS U01 NS058162NINDS NIH HHS U01 NS102135
6 · The paper itself

Abstract

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2mg/kg, administered 20 min after soman exposure (1.2×LD50), terminated seizures. ATS at 0.5mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1h post-exposure, prevents brain pathology and behavioral deficits.

Indexed as

AcetylcholinesteraseAnimalsAnticonvulsantsAtropineChemical Warfare AgentsCholinesterase InhibitorsDisease Models, AnimalHippocampusIsoquinolinesKainic Acid ReceptorsMaleNerve DegenerationOximesRandom AllocationRatsRats, Sprague-DawleyAcetylcholinesteraseAnticonvulsantsAtropineChemical Warfare AgentsCholinesterase InhibitorsIsoquinolinesKainic Acid ReceptorsOximesSomanTetrazolestezampanelAcetylcholinesteraseAtropine sulfateGluK1 antagonistsImmature ratsSeizuresSoman

Identifiers

PMID25689173
PMCPMC4545593
OpenAlexW2075217951

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.